In order to understand the organization and functions of the genome of an oncogenic adenovirus, conditional lethal mutants will be isolated and characterized. We hope to study the genetic control of oncogenic adenovirus development by identifying which essential genes must function early and late during adenovirus development in tissue culture cells undergoing cytocidal infection. In addition, the study of conditional lethal virus mutants may provide direct evidence that malignant transformation in vitro is caused by one or more functions of the adenoviral genes, by establishing which gene product(s) must be present to produce and maintain the transformation. Through the coupling of biochemical and genetic studies, we will attempt to attain an understanding of the mechanism of virus reproduction, as well as of oncogenicity, on a molecular level.